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BACKGROUND@#High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.@*OBJECTIVE@#The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.@*DESIGN, PARTICIPANTS AND INTERVENTION@#This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.@*MAIN OUTCOME MEASURES@#The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.@*RESULTS@#A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.@*CONCLUSION@#STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.@*TRIAL REGISTRATION@#This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.
Assuntos
Animais , Humanos , Masculino , Camundongos , Difosfato de Adenosina , Angina Instável/induzido quimicamente , Biomarcadores , Clopidogrel , Citocromo P-450 CYP2C19/genética , Medicamentos de Ervas Chinesas , Galectina 3 , Molécula 1 de Adesão Intercelular , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Molécula 1 de Adesão de Célula Vascular/genéticaRESUMO
Objective :To explore influence of oxidized low density lipoprotein (ox-LDL ) on migration function of THP-1 macrophages ,expression of microRNA 21 (miR-21) and mitogen-activated protein kinase (MAPK) path-way.Methods :Phorbol myristate acetate (PMA) of 160nmol/L was used to induce THP-1 cells to differentiate into macrophages.According to application of ox-LDL treatment and liposomes-mediated miR-21 inhibitor transfecting THP-1 macrophages (transfection for short) or not ,THP-1 macrophages were divided into blank control group (re-ceived neither ox-LDL treatment nor transfection ) ,ox-LDL group (received 50mg/L ox-LDL treatment without transfection) ,miR-21 inhibitor group (received 50mg/L ox-LDL treatment after transfection ) and miR-21 inhibitor negative-control group (received 50mg/L ox-LDL treatment after negative-control transfection ).THP-1 macro-phage migration number was measured by transwell method ,miR-21 expression was measured by real-time quantita-tive PCR ,and expression of dual specific phosphate 8 (DUSP-8) and phosphorylation level of MAPK pathway were measured by Western-blot method .Results :Compared with blank control group ,there were significant rise in mi-gration number of THP-1 macrophages [(74.10 ± 15.10) vs.(184.10 ± 26.28)] ,miR-21 expression [(1.00 ± 0.21) vs.(2.02 ± 0.27)] and phosphorylation levels of JNK and P38 protein ,and significant reduction in expression of DUSP-8 protein in ox-LDL group ,P<0.01 all.Compared with ox-LDL group ,there were significant reductions in migration number of THP-1 macrophages [ (184.10 ± 26.28) vs.(58.50 ± 10.24)] ,miR-21 expression [ (2.02 ± 0.27) vs.(0.66 ± 0.16)] and phosphorylation levels of JNK and P38 protein ,and significant rise in expression of DUSP-8 protein in ox-LDL group , P<0. 01 all .Conclusion : Ox-LDL enhances migration function of macrophages , which may be related to its effects of upregulating miR-21 expression ,enhancing phosphorylation of JNK and P38 protein of MAPK pathway and reducing DUSP-8 expression .
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Objective: To analyze the changes of chemical ingredients before and after compatibility of Aconiti Lateralis Radix Praeparata (ALRP) and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (GRRPM), and to explore the possible mechanism of toxicity attenuation of their compatibility. Methods: The chemical ingredients in the decoction of ALRP and the decoction of compatibility of ALRP and GRRPM were comparatively researched by HPLC-MS. Single decoction of ALRP and compound decoction of compatibility of ALRP and GRRPM were prepared, and their HPLC-MS fingerprints were respectively established and determined by Q-TOF/MS under the same condition. Results: Twenty ingredients and their structures were identified from single decoction of ALRP; 32 ingredients and their structures were indentified from the decoction of ALRP and GRRPM, among them 4 from GRRPM, 28 from ALRP. And the alkaloid categories and contents of ALRP were significantly different before and after the compatibility with GRRPM. Conclusion: The compatibility with GRRPM could change the alkaloid composition in ALRP, which provides the experimental evidences for the toxicity attenuation mechanism of compatibility of ALRP and GRRPM.
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Objective To observe the mechanical allodynia of affected extremity and the leakage of Evans blue when performing thermal stimulation on the threshold, and explore the efficacy of microwave on rats models of neuropathic pain and the optimum temperature and other ideal parameters for this treatment by performing microwave coagulation treatment under different temperatures to them.Methods Forty-two SD rats were induced the models of spared nerve injury (SNI) on sciatic nerves,then were equally randomized into 3 groups: control group (only inserting microwave coagulation needle but not heating), 42℃ microwave coagulation treatment group and 60℃ microwave coagulation treatment group (n=14). The 50% paw withdrawal threshold of the affected extremity was measured 1 d before and 1, 2, 4, and 6 weeks after treatment. The leakage of Evans blue in injured tissue of the affected extremity when performing thermal stimulation on the threshold was observed 2 weeks after treatment and compared between each 2 groups. Results The 50% paw withdrawal threshold was stable in control group, 42℃ microwave coagulation treatment group and 60℃ microwave coagulation treatment group 1 d before treatment; no significant differences were noted between each 2 groups (P>0.05). The 50% paw withdrawal threshold of 60℃ microwave coagulation treatment group 1, 2, 4, 6weeks after treatment was significantly increased as compared with that in the control group and 42℃microwave coagulation treatment group (P<0.05). The concentrations of leakage of Evans blue in the 42℃ microwave coagulation treatment group ([9.96±1.01] g/g) and 60℃ microwave coagulation treatment group ([7.41±1.37] g/g) were significantiy decreased as compared with those in the control group ([14.8±2.88] g/g, P<0.05). Conclusion Microwave coagulation can improve the mechanical hyperalgesia of in rats with neuropathic pain induced by SNI, and 60℃ is the proper temperature.Inflammation is inhibited by microwave coagulation and this might be one of the mechanisms to alleviate the pain.
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To increase drug concentration in the head through intranasal administration, we have investigated the excised animal nasal mucosa permeability and nasal toxicity of the baicalin drug carrier systems, such as baicalin liposomes, beta-cyclodextrin inclusion compound, and phospholipid complex. A transport of baicalin drug carrier systems through nasal mucosa was simulated in diffusion chamber in vitro, and swine, caprine and rabbit nasal mucosa was used, the concentration of drug in the receptor was determined by HPLC. By taking the apparent permeability coefficients as evaluation standard, investigated the isolated animal nasal mucosa permeability of different baicalin drug systems was investigated for screening the best baicalin drug carrier system through nasal cavity administration. Toxicity of baicalin and its phospholipids complex on toad palate mucosal cilia movement and rats nasal mucosa long-term toxicity were studied in vivo. The apparent permeability coefficient of three kinds of baicalin drug carrier systems was better than that of baicalin (P < 0.05), and its lag-time was obviously shortened. At the same time, the apparent permeability coefficient of phospholipid complex was higher than those of other two drug carrier systems (P < 0.05). The results showed that the baicalin phospholipids complex nasal mucosa permeability was obviously superior to the other two drug systems. Baicalin phospholipids complex had no toxicity to ciliary movement, and had no irritation to rat nasal mucosa. The results show that baicalin phospholipid complex was the best baicalin drug carrier system, it could significantly enhance the permeability of baicalin across nasal mucosa, had no toxicity to nasal mucosa, and could be used for intranasal administration.